January 24, 2012
IPET method is under the spotlight. The News has been released on the front page of LBNL website.

January 24, 2012
IPET reconstruction method for determining the structure an individual protein is published by PLoS One , [pdf download]

IPET: an approach for studying the flexible proteins structure via 3-D imaging of a single protein

Proteins play many key roles in activity of cell and body through their unique 3-D structures and structural changes. Many techniques have been developed maturely to determine their unique 3-D structure. However, the nature character of structural changes and dynamics was rarely discussed. In fact, the structure changes are essential for their function and activities.

Current techniques (including X-ray and cryo-EM) have their limitation in revealing the protein structural dynamics and fluctuations due to a common method used, i.e. averaging thousands to millions different particles for 3-D structure determination. Scientifically speaking, no one can guaranty the averaged particles are sharing an identical same structure before conducting the averaging process. Practically speaking, only small amount of proteins that are naturally having a ridge-body structure that can be averaged for high resolution 3-D, a large amount of proteins that naturally flexible and dynamics are not sharing a same structure often cause the failure in obtaining a high-resolution 3-D average. Since the failure of averaging cannot be published, it generated a public impression that the proteins are all alike the "statue of liberty" instead of its original model, an Arab woman who has her movable arms.

The research objective in this laboratory is focused on developing a so-called individual-particle electron tomography (IPET) for 3-D structure determination based on each targeted single particle of protein (no averaging from different particles) at an intermediate-resolution (1-3 nm). Although the signal from a single particle of protein is widely believed insufficiently to be used to achieve a 3-D structure at a resolution that is able to address any biological questions, in science, there is no proof of contradiction as an impossibility proof.

Continually developing this technique to achieve high-resolution 3-D structures from a single targeted protein is expected to be an ultimate method for revealing the protein flexible structure in 3-D and tracking the 3-D conformational changes during their activities. The method can also avoid the weakness and potential artifacts in the averaging method, such as the smeared/eliminated densities of the protein flexible domains and the anisotropic resolutions in the 3-D.